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LINC00675 Suppresses Cell Proliferation and Migration via Downregulating the H3K4me2 Level at the SPRY4 Promoter in Gastric Cancer.


ABSTRACT: Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are dysregulated in diverse tumors and take a pivotal role in modulating biological processes. In our study, a decreased expression level of LINC00675 in gastric cancer (GC) was first determined by data from The Cancer Genome Atlas (TCGA) and was identified using specimens from GC patients. Then, in vitro and in vivo functional experiments elaborated that LINC00675 could suppress cell proliferation and migration in GC. Multiple differentially expressed genes (DEGs) in LINC00675-overexpressing cells were identified through RNA sequencing analysis. An RNA-binding protein immunoprecipitation (RIP) assay was conducted to reveal that LINC00675 competitively bound with lysine-specific demethylase 1 (LSD1). A coimmunoprecipitation (coIP) assay indicated that LINC00675 overexpression may strengthen the binding of LSD1 and H3K4me2, whereas the chromatin immunoprecipitation (ChIP) assay results verified lower expression of H3K4me2 at the sprouty homolog 4 (SPRY4) promoter region. Together, our research identified that LINC00675 was remarkably downregulated in GC tissues and cells relative to nontumor tissues and cells. LINC00675 could repress GC tumorigenesis and metastasis via competitively binding with LSD1 and intensifying the binding of LSD1 and its target H3K4me2. Importantly, this contributed to attenuated binding of H3K4me2 at the promoter region of oncogene SPRY4 and suppressed SPRY4 transcription, thus suppressing GC cell proliferation and migration.

SUBMITTER: Pan Y 

PROVIDER: S-EPMC7595884 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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LINC00675 Suppresses Cell Proliferation and Migration via Downregulating the H3K4me2 Level at the SPRY4 Promoter in Gastric Cancer.

Pan Yutian Y   Fang Yuan Y   Xie Mengyan M   Liu Yu Y   Yu Tao T   Wu Xi X   Xu Tongpeng T   Ma Pei P   Shu Yongqian Y  

Molecular therapy. Nucleic acids 20201004


Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are dysregulated in diverse tumors and take a pivotal role in modulating biological processes. In our study, a decreased expression level of LINC00675 in gastric cancer (GC) was first determined by data from The Cancer Genome Atlas (TCGA) and was identified using specimens from GC patients. Then, <i>in vitro</i> and <i>in vivo</i> functional experiments elaborated that LINC00675 could suppress cell proliferation and migration in  ...[more]

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